The present invention relates to a radioactive balloon for angioplasty which is combined with a flexible film containing radionuclides and process for preparation thereof, which can prevent vascular restenosis efficiently.
Percutaneous transluminal coronary angioplasty has been operated to treat coronary-stenosing diseases such as arteriosclerosis and the like. The angioplasty was first performed in human body by Gruenzig et al. in 1977 and has been firmly established as a curative method for treating coronary diseases. Presently, 500,000 people per year have been reported to be treated with the method worldwidely (Holmes, D. R. et al., Am. J. Cardiol., 53: 77C-81C, 1984). In Korea the angioplasty has also been performed actively, especially at the university hospitals.
Since operational apparatuses for the percutaneous transluminal coronary angioplasty were developed diversely, the angioplasty has been widely performed so as to be applied to various diseases. Practically, the angioplasty has been operated in single vessel disease and multiple vessel disease, stable angina pectoris and instable angina pectoris, acute myocardial infarction and the like (Nobuyoshi, M. et al., J. Am. Coll. Cardiol., 17: 198B, 1991; Waller, B. F. et al., J. Am. Coll. Cardiol., 17: 58B-70B, 1991).
Although the angioplasty treated by using the balloon dilatation catheter, etc. succeeded clinically at the rate of 95%, but acute closure and restenosis can be induced before and after the operations.
The restenosis described above may be induced by the mechanisms such as the vascular remodeling, the proliferation of the injured smooth muscle cell (SMC), the formation of extracellular matrix and the like (Wither, H. R. et al., Cancer, 34: 39-47, 1974; Thames, H. D. et al., Int. J. Radiat. Onco. Biol. Phys., 7: 1591-1597, 1981). Although the smooth muscle cell within the vessel is not proliferative normally, physical defects and stimuli incites smooth muscle cell to migrate into the inner layer of blood vessel, to multiply or to form a matrix tissue.
In early days of coronary angioplasty, such a restenosis occurred in approximately 30-45% of patients. New methods such as atherectomy, rotabulation, use of transluminal extraction catheter (TEC), excimer laser coronary angioplasty and insertion of stent have been accomplished in order to reduce the restenosis rate.
The above methods were also performed clinically by using anti-thrombocyte agent, anti-coagulant, steroids, calcium channel blocker, colchicine, etc. in order to prevent the restenosis. But effective drugs reducing the restenosis has not yet been discovered. Recently, local drug delivery and gene therapy also are being performed a lot, which shows good effects in in vitro study, but the effects were uncertain in in vivo study. Since blood flows through the blood vessel fast and washes off the above drugs, such a treatment is not effective. Especially, it is more difficult to administer the drugs at the specific sites of the blood vessel.
As described above at the restenosed sites, lesions of the blood vessel also induces neointimal hyperplasia. In this case, local radiation can decrease the number of progenitor cells in regenerating tissues.
It is reported that ionizing radiation inhibits the thymidine uptake and the collagen synthesis in cultured fibroblast and can be used effectively at a low dosage for preventing proliferative lesions or keloids which are formed after the surgical operation. At that time, about 10 Gy (1,000 rad) of radiation may be irradiated for the treatment, which does not affect the general treatment process.
Practically, the insertion of metallic stent is a general method to prevent the restenosis which is induced after operating the transluminal coronary angioplasty in artery-restenosing diseases. In place of the simple metallic stent, radioactive stents coated with radionuclides such as Ir-192, Y-90, P-32 and the like have been developed to inhibit the proliferation of smooth muscle cell fundamentally. Radioactive rays emitted from the stents destruct the multiplying cells, and this is exploited to prevent the restenosis actively.
However, after the insertion of the stent, the amount of radioactivity can not be adjusted according to the change of the patient""s state. In order to settle the shortcomings, a minimally invasive medical device for providing the radiation treatment has been designed (U.S. Pat. No. 5,484,384). Precisely, the medical device comprises a outer sheath, a wire coil and a flexible elongated member having distal and proximal portion which can slide through the sheath. The device also contains radioactive isotopes at the elongatable distal portion and can be utilized for the radiation therapy controlling the radioactivity.
In addition, an invasive medical device has been designed, which is combined with a sleeve containing radioactive isotopes which is dispersed and adhered onto the wire coil. In detail, the device comprises an elongatable distal portion, an expandable balloon and a catheter and can irradiate the wall of the blood vessel wall by expanding the wall of the balloon with radioactive liquid instead of gas (Fearnot, U.S. Pat. No. 5,484,384, 1996).
In order to irradiate a lesion site evenly, radioactive material should fill the balloon for expanding. However, when the balloon ruptures during the angioplasty, radioactive material may be absorbed into human body which causes serious danger. When beta-ray emitting nuclides are used, the restenosing site in the blood vessel wall can be irradiated only by radioactive material which is in contact with the surface of the inner space of the balloon since it has a short transmitting distance. Thus other radioactive materials within the inner space of the balloon can not be utilized for the irradiation and are lavished on the expansion only.
In order to settle the shortcomings, a balloon dilatation catheter system consisting of 2 balloons has been developed. In the catheter system, an inner balloon is used to expand the system and an outer balloon, to fill the radioactive material (such as I-125, P-32), so as to reduce the lavished radioactivity and improve safety problems (Bradshaw, et al., U.S. Pat. No. 5,662,580, 1997). In addition, a balloon dilatation catheter system which exploits radioactive capsule or pellet, suspended in liquid for filling the balloon has been established for the radiation therapy (Waksman, et al., U.S. Pat. No. 5,683,345, 1997).
However, radioactive balloon dilatation catheter system with 2-layered balloons or the system including radioactive capsule or pellets are both not safe when the outer balloon is disrupted. The disruption releases radioactive material into the body and so it gets irradiated. Furthermore, the process for preparing the catheter system is too difficult and complex to be performed.
Therefore, in order to overcome the above problems of the general radioactive balloon, the present inventors have developed new balloon dilatation catheter system which can prevent the restenosis efficiently after the transluminal coronary angioplasty. To be precise, radioactive balloon used in this catheter system has been prepared by mixing radionuclides with carrier material, immersing the balloon into the mixed solution and drying it so as to produce the balloon surface coated with radioactive film. The balloon dilatation catheter system exploiting the balloon inhibits the restenosis in vascular restenosing diseases effectively.
The object of the present invention is to provide a radioactive balloon of balloon dilatation catheter which is surrounded with a flexible film containing radionuclides for preventing restenosis after the treatment of vascular restenosing diseases.
The present invention provides a radioactive balloon which is surrounded with a flexible film containing radionuclides and used in balloon dilatation catheter.
The present invention provides the radioactive balloon which utilizes Sm-153, Dy-165, Ho-166, Er-169, P-32, Y-90, I-131, Re-186, Re-198, Pd-109 or Au-198 as beta-ray emitting nuclide and Ir-192, Co-57, Co-60, V-48 or I-125 as gamma-ray emitting nuclide.
The object of the present invention is to provide processes for preparing the radioactive balloon.
The present invention provides a process for preparing the radioactive balloon which comprises;
(S1) immersing the balloon of the balloon dilatation catheter in solution containing radionuclide compound, and
(S2) maintaining the above balloon in a horizontal position and drying it to form a film layer.
The present invention provides uses of the balloon dilatation catheter containing the radioactive balloon for treating the angiostenosis found in vascular disease such as arteriosclerosis.